Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double-blind RCT in 262 chronic smokers meeting DSM-5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat-eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue-induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four-week continuous quit rate (CQR) until Week 18 in the intent-to-treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent-to-treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X2 =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2 =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok-ing cessation for adults.

Beneficial effects of caloric vestibular stimulation on denial of illness and manic delusions in schizoaffective disorder: a case report.

INTRODUCTION: Preliminary data suggests that caloric vestibular nerve stimulation (CVS) single session application of cold water to the left ear induces a clinically significant, short-lived beneficial effect on specific types of illness denial (i.e., anosognosia) and delusions (i.e., somatic type). METHODS: We recently studied the effect of left versus right ear ice water (4°C) CVS on delusions and insight of illness in a patient with manic episode due to schizoaffective disorder. The patient was evaluated at baseline, immediately after the CVS, and then at 20 minutes, 60 minutes, and 24 hours. The method was first applied to one ear and 4 days later to the other. To assess whether the effect is specific to mania we employed the same procedure in two other patients with schizophrenia who also demonstrated delusions and impaired insight. RESULTS: All three patients showed a difference favoring left versus right ear CVS that was maintained for 20 minutes, and diminished over a 60 minute period. EEG analyses showed a numerically non-significant increase in bilateral frontal and central alpha EEG band activation (more pronounced in the right hemisphere) with left but not right ear CVS 5 minutes after the CVS, and that diminished after 20 minutes. DISCUSSION: The results suggest that left versus right CVS may have a short lived beneficial effect on manic delusions and insight of illness that seem to appear in other types of psychoses (i.e., schizophrenia). CONCLUSION: These preliminary results suggest that single session CVS may have short lived beneficial effects in mania and perhaps in other types of psychoses. Further research is mandatory.

Cognitive rigidity in unipolar depression and obsessive compulsive disorder: examination of task switching, Stroop, working memory updating and post-conflict adaptation.

Obsessive compulsive disorder (OCD) and depressive rumination are both characterized by cognitive rigidity. We examined the performance of 17 patients (9 suffering from unipolar depression [UD] without OCD, and 8 suffering from OCD without UD), and 17 control participants matched on age, gender, language and education, on a battery covering the four main executive functions. Results indicated that, across both disorders, patients required more trials to adjust to single-task conditions after experiencing task switching, reflecting slow disengagement from switching mode, and showed abnormal post-conflict adaptation of processing mode following high conflict Stroop trials in comparison to controls. Rumination, which was elevated in UD and not in OCD, was associated with poor working memory updating and less task preparation. The results show that OCD and UD are associated with similar cognitive rigidity in the presently tested paradigms.

The effect of sudden clozapine discontinuation on management of schizophrenic patients: A retrospective controlled study.

BACKGROUND: The aims of our study were (1) to compare the dose of clozapine needed to achieve remission in patients who stopped their treatment (study group) versus patients who continued taking this medication (control group) and (2) to compare the clinical characteristics of remission between these 2 groups. METHOD: We retrospectively reviewed the medical records of all treatment-resistant schizophrenic and schizoaffective patients (according to DSM-IV criteria) who were treated with clozapine over a period of 9 years, from January 1995 through December 2003. The study group consisted of 43 patients and the control group of 12 patients. All patients' files from both groups were examined, and each patient's remission was scored twice--initially on discharge from the hospital and subsequently after final discharge for the study group, or at the end of the study for the control group. RESULTS: The change of clozapine dose from the first to the last remission expressed by percentage shows a significant difference between the 43% increase in clozapine dose in the study group and the 12.5% decrease in clozapine dose in the control group (p < .001). Quality of remission assessment showed deterioration in the global remission score in the study group, while the quality of remission assessment in the control group did not show any change. CONCLUSIONS: Our findings suggest that the discontinuation of clozapine treatment leads to a deterioration in the quality of remission, with a need for an increased dose of clozapine. Further prospective studies on larger samples are needed to confirm these findings.